Ontogeny of Central Neural Taste Responses

项目总结/摘要 味觉系统的发展以结构和功能的变化为特征。中央 啮齿类动物的味觉通路在正常发育过程中尤其可塑，甚至在第一次突触传递时也是如此。 在结构上，终端（即，终端领域）的神经元进行味觉信息从味蕾到 延髓中的孤束核（NST）的大小减小，或“修剪”，约为它们大小的一半-- 在断奶前开始，并在断奶后持续约10天。在功能上， “修剪”与味觉神经中味觉引起的神经活动的增加同时发生，这表明 必要的活动依赖的组成部分。此外，对神经活动的实验操作和 动物在发育过程中的饮食史中断了终端领域的正常“修剪”，表明， 活动依赖性和活动非依赖性因素都在回路的发育过程中起作用 精致。这个项目的长期目标是了解中央味觉系统是如何组装的 然后通过经验来提炼。这项提案的具体目标是研究1）神经元如何支配 舌头前2/3上的单个味蕾映射到NST上，以及在NST期间投射如何变化。 正常发育的成年小鼠和在整个发育过程中神经活动改变的成年小鼠中， 饮食史，以及2）在正常发育过程中神经免疫分子级联是如何运作的， 在神经活动改变或饮食史改变的小鼠中中断。该项目的目标将是 通过单一味蕾标签、外周味觉神经记录、中枢味觉神经记录和味觉神经记录的协调技术来解决。 神经系统束示踪，在光镜和电镜下对突触元件进行广泛分析 水平和功能实验的光遗传学恢复。这些研究将提供新的和重要的 关于中枢味觉系统的发展和可塑性的信息， 免疫和味觉系统在发展过程中，更广泛地说，他们将是有用的，在确定 母亲的饮食和味觉诱发活动对组织味觉发育的作用。

Project Summary/Abstract The developing gustatory system is characterized by impressive structural and functional changes. The central taste pathway in rodents is especially plastic during normal development, even at the first synaptic relay. Structurally, the terminations (i.e., terminal fields) of neurons carrying taste information from taste buds to the nucleus of the solitary tract (NST) in the medulla are reduced in size, or “pruned”, to about half of their size -- beginning just before weaning and extending for about 10 days after weaning. Functionally, the period of “pruning” occurs coincident with the increase in taste-elicited neural activity in gustatory nerves, suggesting a requisite activity-dependent component. Moreover, experimental manipulations of neural activity and the animal’s dietary history during development interrupts the normal “pruning” of terminal fields, indicating that both activity-dependent and activity-independent factors play a role in the developmental process of circuit refinement. The long-term goal of this project is to understand how the central gustatory system is assembled and then refined by experience. The specific aims of this proposal examine 1) how neurons that innervate single taste buds on the anterior 2/3 of the tongue map onto the NST and how the projections change during normal development and in adult mice that have altered neural activity throughout development or an altered dietary history, and 2) how the neuro-immune molecular cascade operating during normal development is interrupted in mice that have altered neural activity or an altered dietary history. The aims of the project will be addressed through coordinated techniques of single taste bud labels, peripheral taste nerve recordings, central nervous system tract tracing, extensive analyses of synaptic elements at the light and electron microscopic level, and optogenetic recovery of function experiments. These studies will provide new and important information about the development and plasticity of the central gustatory system, the interplay between the immune and gustatory systems during development, and more broadly, they will be useful in determining the role that the maternal diet and taste-elicited activity have on organizing the developing sense of taste.